Genetic Variant CDKN2B-AS1:n.372-1881C>T (chr9-22027552-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000428597.7(CDKN2B-AS1):n.372-1881C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 152,240 control chromosomes in the GnomAD database, including 62,806 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.91 ( 62806 hom., cov: 33)

Consequence

CDKN2B-AS1
ENST00000428597.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.505

Publications

14 publications found

Variant links:

Genes affected

CDKN2B-AS1 (HGNC:34341): (CDKN2B antisense RNA 1) This gene is located within the CDKN2B-CDKN2A gene cluster at chromosome 9p21. The gene product is a functional RNA molecule that interacts with polycomb repressive complex-1 (PRC1) and -2 (PRC2), leading to epigenetic silencing of other genes in this cluster. This region is a significant genetic susceptibility locus for cardiovascular disease, and has also been linked to a number of other pathologies, including several cancers, intracranial aneurysm, type-2 diabetes, periodontitis, Alzheimer's disease, endometriosis, frailty in the elderly, and glaucoma. Multiple alternatively processed transcript variants have been detected, some of which may take the form of circular RNA molecules (PMID:21151960). [provided by RefSeq, May 2014]

CDKN2B-AS1 links:

ENSG00000264545 (HGNC:):

ENSG00000264545 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
CDKN2B-AS1	NR_003529.4 link	n.372-1881C>T	intron_variant	Intron 1 of 18
CDKN2B-AS1	NR_047532.2 link	n.372-1881C>T	intron_variant	Intron 1 of 13
CDKN2B-AS1	NR_047533.2 link	n.372-19199C>T	intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CDKN2B-AS1	ENST00000428597.7 link	n.372-1881C>T	intron_variant	Intron 1 of 18	1
CDKN2B-AS1	ENST00000455933.8 link	n.341-19199C>T	intron_variant	Intron 1 of 4	1
CDKN2B-AS1	ENST00000577551.5 link	n.261-19199C>T	intron_variant	Intron 1 of 6	1

Frequencies

GnomAD3 genomes

AF:

0.908

AC:

138183

AN:

152122

Hom.:

62766

Cov.:

show subpopulations

Gnomad AFR

AF:

0.903

Gnomad AMI

AF:

0.955

Gnomad AMR

AF:

0.921

Gnomad ASJ

AF:

0.904

Gnomad EAS

AF:

0.981

Gnomad SAS

AF:

0.952

Gnomad FIN

AF:

0.916

Gnomad MID

AF:

0.867

Gnomad NFE

AF:

0.899

Gnomad OTH

AF:

0.909

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.908

AC:

138280

AN:

152240

Hom.:

62806

Cov.:

AF XY:

0.910

AC XY:

67721

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.903

AC:

37502

AN:

41544

American (AMR)

AF:

0.921

AC:

14098

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.904

AC:

3137

AN:

3470

East Asian (EAS)

AF:

0.980

AC:

5073

AN:

5174

South Asian (SAS)

AF:

0.952

AC:

4586

AN:

4818

European-Finnish (FIN)

AF:

0.916

AC:

9713

AN:

10602

Middle Eastern (MID)

AF:

0.867

AC:

255

AN:

294

European-Non Finnish (NFE)

AF:

0.899

AC:

61126

AN:

68014

Other (OTH)

AF:

0.910

AC:

1921

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

669

1338

2007

2676

3345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.900

Hom.:

26678

Bravo

AF:

0.910

Asia WGS

AF:

0.955

AC:

3318

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

5.6

(source)

DANN

Benign

0.34

PhyloP100

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over